Gene and protein expression in the oxaliplatin-resistant HT29/L-OHP human colon cancer cell line

Xiang, Zheng; Kang, Qingjie; Xiang, Xinxin

doi:10.4238/2015.september.21.14

Cited by 11 publications

(8 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, increased expression of the inhibitor of apoptosis BIRC4 (XIAP) could also contribute to oxaliplatin resistance and counteract the increased expression of the cell death execution caspases 6 and 7 in the platinum-resistant ovarian cancer cell lines. These data are in line with the decrease in annexin A3 in l-OHP resistant colon cancer cells [43], as well as an activation of mutated p53 in l-OHP resistant ovarian cancer cells [44] and a change in multiple apoptosis regulating genes in resistant colon cancer cells [45].…”

Section: Discussionsupporting

confidence: 71%

Coexisting Molecular Determinants of Acquired Oxaliplatin Resistance in Human Colorectal and Ovarian Cancer Cell Lines

Noordhuis

Laan

Born

et al. 2019

IJMS

View full text Add to dashboard Cite

Oxaliplatin (OHP) treatment of colorectal cancer (CRC) frequently leads to resistance. OHP resistance was induced in CRC cell lines LoVo-92 and LoVo-Li and a platinum-sensitive ovarian cancer cell line, A2780, and related to cellular platinum accumulation, platinum-DNA adducts, transporter expression, DNA repair genes, gene expression arrays, and array-CGH profiling. Pulse (4 h, 4OHP) and continuous exposure (72 h, cOHP) resulted in 4.0 to 7.9-fold and 5.0 to 11.8-fold drug resistance, respectively. Cellular oxaliplatin accumulation and DNA-adduct formation were decreased and related to OCT1-3 and ATP7A expression. Gene expression profiling and pathway analysis showed significantly altered p53 signaling, xenobiotic metabolism, role of BRCA1 in DNA damage response, and aryl hydrocarbon receptor signaling pathways, were related to decreased ALDH1L2, Bax, and BBC3 (PUMA) and increased aldo-keto reductases C1 and C3. The array-CGH profiles showed focal aberrations. In conclusion, OHP resistance was correlated with total platinum accumulation and OCT1-3 expression, decreased proapoptotic, and increased anti-apoptosis and homologous repair genes.

show abstract

Section: Discussionsupporting

confidence: 71%

Coexisting Molecular Determinants of Acquired Oxaliplatin Resistance in Human Colorectal and Ovarian Cancer Cell Lines

Noordhuis

Laan

Born

et al. 2019

IJMS

View full text Add to dashboard Cite

show abstract

“…In many cases, extensive DNA damage leads to activation of cell cycle check points and results in cell cycle arrest and apoptosis (32). Previous studies have shown that ACBP promoted cell proliferation in GC cells and inhibited MGC-803 cancer cells (17) and L-OHP-resistant human colon cancer cell lines with increasing dose of L-OHP in culture (33). In this study, we found that A+L induced apoptosis in MKN-45 cells, which was revealed by the PI assay.…”

Section: Discussionsupporting

confidence: 62%

New bioactive peptide reduces the toxicity of chemotherapy drugs and increases drug sensitivity

Ouyang

et al. 2017

Oncology Reports

View full text Add to dashboard Cite

Anticancer bioactive peptide (ACBP) is extracted from normal goat spleens and exhibits antitumor activity alone and in combination with low cisplatin doses to achieve antitumor efficacy similar to higher cisplatin doses via sustained medication modes. In the present study, we investigated whether elevated levels of induced or normal ACBP in MKN‑45 gastric cancer (GC) cells may reduce their toxicity to oxaliplatin (L‑OHP) in a dose‑dependent manner. The growth inhibition rate (IR), morphological changes and gene expression were examined in MKN‑45 GC cells. Compared with normal ACBP, induced ACBP alone significantly enhanced the anticancer activity of L‑OHP‑mediated apoptosis and reduced the amount and side‑effects of L‑OHP (P<0.05). The inhibition of cancer cell growth at high concentrations of induced ACBP and L‑OHP was significantly more effective than at low concentrations. In addition, for the first time, we examined the potential of a combination of induced ACBP and L‑OHP to increase L‑OHP sensitivity in human gastric carcinoma xenograft tumors. Nude mice were implanted with human gastric carcinoma MKN‑45 cells and treated with an intraperitoneal injection of 0.5 ml of normal saline, 30 µg/ml ACBP, 20 µg/ml L‑OHP or 30 µg/ml ACBP + 20 µg/ml L‑OHP [combination of anticancer bioactive peptide and oxaliplatin (A+L)] via the tail vein twice a week. In vivo short‑term intermittent use of induced ACBP alone significantly inhibited MKN‑45 tumor growth. The combination of induced ACBP and L‑OHP also significantly improved the quality of life of the nude mice and reduced the toxicity of L‑OHP. Based on flow cytometry and gene expression analyses, A+L significantly increased the proportion of cells in the G2/M phase (P<0.05) relative to ACBP or L‑OHP alone, and short‑term intraperitoneal injection of ACBP increased the sensitizing effect of L‑OHP. Collectively, these results suggest that high levels of induced ACBP in combination with L‑OHP via a short‑term intermittent medication mode could be a useful clinical therapeutic strategy for GC.

show abstract

“… 38 – 40 The result showed that the L-OHP–resistant cell line acquired resistance to apoptosis by activation of PI3K/AKT signaling pathway, upregulation of Bcl-2 and downregulation of Bax. 41 The inactivated PI3K/AKT signaling pathway promoting apoptosis induced a reduction of the Bcl-2/Bax ratio, eventually triggering caspase-3 activation and inducing apoptosis. 42 Similarly, we found that knockdown of KLK11 inactivated the PI3K/AKT signaling pathway, increased the Bax expression, and decreased the Bcl-2 expression, which led to a reduction of the Bcl-2/Bax ratio.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of KLK11 reverses oxaliplatin resistance by inhibiting proliferation and activating apoptosis via suppressing the PI3K/AKT signal pathway in colorectal cancer cell

Zhang¹,

Xu²,

Sun³

et al. 2018

OTT

View full text Add to dashboard Cite

IntroductionKallikrein 11 (KLK11) plays a crucial role in drug-resistance to oxaliplatin (L-OHP) in the treatment of metastatic colorectal cancer (mCRC). The study aimed to investigate the role of KLK11 in chemoresistance, and to clarify the mechanism underlying reverse of L-OHP resistance by knockdown of KLK11.Materials and MethodsResistance to oxaliplatin was induced in HCT-8 (HCT-8/L-OHP) colorectal adenocarcinoma cell lines by exposing cells to increasing concentrations of L-OHP. MTT, RT-qPCR, and Western blot were used to evaluate the resistance to L-OHP. We then knocked down KLK11 in HCT-8/L-OHP cells to explore the mechanism through which KLK11 reverses L-OHP resistance. The mRNA and protein expression of KLK11 in tissues from mCRC patients were detected by RT-qPCR and immunohistochemistry.ResultsThe drug resistance index (RI) of HCT-8/L-OHP cell line to L-OHP, 5-Fluorouracil (5-FU), Irinotecan (CPT-11), Vincristine (VCR) and Cis-diamminedichloroplatinum (CDDP) were 10, 5.35, 3.23, 1.28, and 6.64, respectively. Increased expression of multi-drug resistant genes ABCC1, ABCB1, GSTP1 and ERCC1 were detected in HCT-8/L-OHP cell line. Moreover, the activated PI3K/AKT pathway was related to L-OHP-resistance. Knockdown of KLK11 in HCT-8/L-OHP cell reversed L-OHP-resistance by inhibiting cell growth and activating apoptosis via suppressing the PI3K/AKT signaling pathway. Moreover, high expression of KLK11 in chemoresistant-patients was associated with lymph node metastases and histopathology.ConclusionKLK11 was highly expressed in chemoresistant-patients and L-OHP-resistant cell lines. Moreover, L-OHP resistance was associated with activated PI3K/AKT signal pathway. Knockdown of KLK11 can reverse L-OHP resistance by blocking PI3K/AKT signaling pathway.

show abstract

Gene and protein expression in the oxaliplatin-resistant HT29/L-OHP human colon cancer cell line

Cited by 11 publications

References 11 publications

Coexisting Molecular Determinants of Acquired Oxaliplatin Resistance in Human Colorectal and Ovarian Cancer Cell Lines

Coexisting Molecular Determinants of Acquired Oxaliplatin Resistance in Human Colorectal and Ovarian Cancer Cell Lines

New bioactive peptide reduces the toxicity of chemotherapy drugs and increases drug sensitivity

Knockdown of KLK11 reverses oxaliplatin resistance by inhibiting proliferation and activating apoptosis via suppressing the PI3K/AKT signal pathway in colorectal cancer cell

Contact Info

Product

Resources

About